Nutritional composition and method for increasing creatine uptake and retention in skeletal muscle, increasing muscle mass and strength, increasing exercise capacity and for aiding recovery following exercise

ABSTRACT

The present invention relates to the composition of a dietary supplement provided for increasing Creatine uptake and retention in skeletal muscle, increasing muscle mass and strength, increasing exercise capacity and aiding in recovery following exercise as well as supporting the immune system during periods of intense training. A method for achieving the same is also provided. The present invention comprises at least Creatine or derivatives thereof, Taurine or derivatives thereof and a source of Phosphate. The dietary supplement may further comprise one or more of the following: Double Fermented  Triticum aestivum , Dextrose, Isomalt, Trehalose, D-Mannose, Mulberry extract,  Enicostemma littorale  Blume,  Scoparia dulcis , Tarragon extract,  Andrographis paniculata , Chromium or derivatives thereof, Glutamine and Alpha Lipoic Acid.

RELATED APPLICATIONS

This application is a continuation of the applicant's co-pending U.S. application Ser. No. 11/552,266, filed Sep. 14, 2006 which in turn claims priority to U.S. Provisional Patent Application Ser. No. 60/776,325 entitled “Compositions and method for increasing bioavailability of compositions for performance improvement”, file Feb. 23, 2006. The entirety of all of these are incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates to the composition of a dietary supplement provided for increasing Creatine uptake and retention in skeletal muscle, increasing muscle mass and strength, increasing exercise capacity and aiding in recovery following exercise as well as providing support for the immune system during intense periods of exercise.

Furthermore, a method for achieving the same by way of administration of the composition is presented.

SUMMARY OF THE INVENTION

The foregoing needs, and other needs and objective which will become apparent for the following description, are achieved in the present invention which comprises a dietary composition and method for enhancing Creatine uptake and retention in skeletal muscle, increasing muscle mass and strength, increasing lean muscle mass, and supporting the immune system of an individual, e.g., a human or an animal during intense training periods. According to an embodiment of the present invention, there are provided compositions and methods which minimize catabolism and promote muscle anabolism, particularly in response to exercise. For example the compositions and methods may allow an individual to increase muscle size, strength or endurance training as well as reduce recovery time and facilitate an increased training volume leading to the same.

According to an embodiment of the present invention, there are provided compositions and methods which comprise at least a combination of Creatine or derivatives thereof, Taurine or derivatives thereof and a source of Phosphate.

According to additional or alternative embodiments of the present invention, there are provided compositions and methods that further comprise at least one of Double Fermented Triticum aestivum, Dextrose, Isomalt, Trehalose, D-Mannose, an extract of Mulberry, Enicostemma littorale Blume, Scoparia dulcis, an extract of Tarragon, Andrographis paniculata, Chromium or derivatives thereof, Glutamine and Alpha Lipoic Acid.

DETAILED DESCRIPTION OF THE INVENTION

In the following description, for the purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of the present invention. It will be apparent, however, to one skilled in the art that the present invention may be practiced without these specific details.

The present invention, according to various embodiments thereof, is directed to a dietary supplement for increasing Creatine uptake and retention in skeletal muscle, increasing muscle mass and strength, increasing exercise capacity and aiding in post-exercise recovery as well as providing support for the immune system during intense exercise training periods. The present invention comprises at least a source of Creatine or derivative thereof, Taurine or derivative thereof and a source of Phosphate. According to various embodiments, the present invention may further comprise combinations of Double Fermented Triticum aestivum, Dextrose, Isomalt, Trehalose, D-Mannose, an extract of Mulberry, Enicostemma littorale Blume, Scoparia dulcis, an extract of Tarragon, Andrographis paniculata, Chromium or derivatives thereof, Glutamine and Alpha Lipoic Acid.

Definitions

As used herein, the term “derivative” refers to a compound, such as a salt, ester, or amine, which can readily supply a closely related biologically active compound, either upon administration or upon exposure to specific environmental conditions, such as pH, temperature, etc. For example, a “derivative” of creatine can be a salt, ester or amine of creatine, so long as the derivative can readily supply biologically active creatine. For a given compound, the skilled person in the art will readily recognize and envisage those closely related compounds which should be considered “derivatives.”

Thus, for example, a derivative of a particular substance may comprise a form of that substance which has been modified through reaction. Other derivatives are forms of a given substance that are precursors of that substance which would give rise to that substance after modification. Reactions involved in the formation of derivatives include, but are not limited to: hydroxylation, esterification, amide formation and salt formation.

As used herein, “Carbohydrate” refers to at least a source of carbohydrates such as, but not limited to, monosaccharides, disaccharides, oligosaccharides, polysaccharides or derivatives thereof.

As used herein, “Creatine” refers to the chemical N-methyl-N-guanyl Glycine, (CAS Registry No. 57-00-1), also known as, (alpha-methyl guanido) acetic acid, N-(aminoiminomethyl)-N-glycine, Methylglycocyamine, Methylguanidoacetic Acid, or N-Methyl-N-guanylglycine. Additionally, as used herein, “Creatine” also includes derivatives of Creatine such as esters, and amides, and salts, as well as other derivatives, including derivatives that become active upon metabolism. Furthermore, Creatinol (CAS Registry No. 6903-79-3), also known as Creatine-O-Phosphate, N-methyl-N-(beta-hydroxyethyl)guanidine O-Phosphate, Aplodan, or 2-(carbamimidoyl-methyl-amino)ethoxyphosphonic acid, is henceforth in this disclosure considered to be a Creatine derivative.

As used herein, “Phosphate” refers to at least a source of Phosphate ions such as, but not limited to, Dipotassium Phosphate, Disodium Phosphate, Magnesium Phosphate or derivatives thereof.

Carbohydrate ingestion is known to stimulate the secretion of insulin which in turn facilitates the uptake of glucose into skeletal muscle via glucose transporter 4 (GLUT4) translocation (Wang et al., J Cell Biol. 1996 135:415-30). Glucose is then converted to and stored as glycogen and triglycerides. Concomitant with this, insulin inhibits the release and synthesis of glucose (Khan et al., Diabetologia. 2002 45:1475-83). Moreover, insulin also plays an important role in protein metabolism where it inhibits the breakdown of protein or proteolysis (Volpi E and Wolfe B. In: Handbook of Physiology, L. Jefferson and A. Cherrington (eds.) New York: Oxford, 2001, p. 735-757; Boirie et al., J Clin Endocrinol Metab. 2001 86:638-44). Furthermore, insulin promotes the uptake of amino acids into muscle and stimulates protein synthesis (Biolo et al., J Clin Invest. 1995 95:811-9), particularly following exercise (Biolo et al., Diabetes. 1999 48:949-57). Insulin has also been shown to stimulate Creatine uptake by muscle cells (Odoom et al., Mol Cell Biochem. 1996 158:179-88). Alpha Lipoic Acid has been shown to have insulin-like properties, which further aid in the retention of Creatine. (Streeper et al., Am J. Physiol. 1997 273(1 Pt 1):E185-91; Ziegler et al., Diabetes Care. 1999 22:1296-301). Via the combination of Creatine with Alpha Lipoic Acid and a small amount of carbohydrate, Creatine retention as compared to Creatine and carbohydrate alone is significantly improved (Burke et al., Int J Sport Nutr Exerc Metab. 2003 13:294-302). Therefore, it is deemed to be advantageous, that for the purposes of Creatine retention, the actions of insulin be enhanced. Furthermore, it may be advantageous to increase the activity and availability of Creatine in skeletal muscle.

Combinations comprising some of the aforementioned ingredients have been shown to offer further benefit to muscle building and increasing strength. In one clinical trial, 32 males were divided into four groups of eight subjects. Group 1 received a combination of Creatine/Dextrose/Taurine/Alpha Lipoic Acid, Group 2 received Creatine plus grape juice, Group 3 received Creatine plus water, and group 4 a placebo. At Day 28 of the experiment, Group 1 had demonstrated greater improvements in body composition and muscular endurance as compared to the other three groups (Kalman et al., Med Sci Sports Exerc. 2000, 32, Supplement abstract 562). In a further study Creatine/Dextrose/Alpha Lipoic Acid was found to provide improved results versus supplementation with whey protein alone in terms of muscle mass gain (Kalman et al., FASEB. 2000, 14:A619). In an eight week study which included diet and weight training, subjects consuming a combination comprising Creatine/Dextrose/Taurine/Ascorbic Acid/Chromium/Alpha Lipoic Acid/Phosphorus gained significantly more mass than subjects consuming Protein/Dextrose alone (Tamopolsky et al., Med Sci Sports Exerc. 2001 33(:2044-52).

Not wishing to be bound by theory, it is herein believed that the activity of insulin initiated by the ingestion of carbohydrates, such as Dextrose as comprised in the present invention, can be enhanced and sustained by insulin potentiators such as, including but not limited to, Taurine, Alpha Lipoic Acid, an extract of Mulberry, Chromium, Glutamine, Enicostemma littorale Blume, Scoparia dulcis, an extract of Tarragon and Andrographis paniculata. In another embodiment, the present invention may comprise one or more of Isomalt, Trehalose or D-Mannose to further potentiate the secretion or activity of insulin. The enhanced activity of insulin may facilitate increased uptake and retention of Creatine, as incorporated into the present invention, by skeletal muscle. Subsequently, the increase in Creatine retention may facilitate increased muscle growth, increased muscle endurance and reduced post-exercise recovery time by virtue of the biological role of Creatine. Furthermore, advantageously, the biological role of Creatine may be aided by ensuring adequate Phosphate availability by the addition of supplemental Phosphates.

Creatine

Creatine is a naturally occurring amino acid derived from the amino acids glycine, arginine, and methionine. Although it is found in meat and fish, it is also synthesized by humans. Creatine is predominantly used as a fuel source in muscle. About 65% of Creatine is stored in muscle as Phosphocreatine (Creatine bound to a Phosphate molecule) (Casey et al., Am J. Physiol. 1996 271:E38-43). Muscular contractions are fueled by the dephosphorylation of adenosine triphosphate (ATP) to produce adenosine diphosphate (ADP) and without a mechanism to replenish ATP stores, the supply of ATP would be totally consumed in 1-2 seconds (Casey and Greenhaff, Am J Clin Nutr. 2000 72:607 S-17S). Phosphocreatine serves as a major source of Phosphate from which ADP is regenerated to ATP. Six seconds following the commencement of exercise, muscular concentrations of Phosphocreatine drop by almost 50% (Gaitanos et al., J Appl Physiol. 1993 75:712-9).

Creatine supplementation has been shown to increase the concentration of Creatine in the muscle (Harris et al., Clin Sci (Lond). 1992 83:367-74) and further said supplementation enables an increase in the resynthesis of Phosphocreatine (Greenhaff et al., Am J. Physiol. 1994 266:E725-30) leading to a rapid replenishment of ATP within the first two minutes following the commencement of exercise.

In the early 1990's it was first clinically demonstrated that supplemental Creatine can improve strength and reduce fatigue (Greenhaff et al., Clin Sci (Lond). 1993 84:565-71). Resistance training with supplemented creatine experiments display a result of increased strength and fat-free mass over a placebo in sedentary females (Vandenberghe et al., J Appl Physiol. 1997 83:2055-63) and in male football players (Vandenberghe et al., J Appl Physiol. 1997 83:2055-63). In addition to increasing fat-free mass and strength, Creatine supplementation increases muscle fiber cross sectional area (Volek et al., Med Sci Sports Exerc. 1999 31:1147-56) thereby increasing muscle volume. High-intensity exercise performance of both males and females is also improved by supplemental Creatine (Tarnopolsky et al., Int J Sport Nutr Exerc Metab. 2000 10:452-63; Burke et al., Int J Sport Nutr Exerc Metab. 2000 10:235-44). Creatine supplementation may also benefit individuals with muscle dystrophy disorders by reducing muscle loss (Walter et al., Neurology. 2000 54:1848-50).

Furthermore, there is evidence that Creatine may have antioxidant properties (Lawler et al., Biochem Biophys Res Commun. 2002 290:47-52; Sestili et al., Free Radic Biol Med. 2006 40:837-49). The antioxidant activity of Creatine may additionally aid post-exercise muscle recovery.

Creatine retention has been shown to be markedly improved by the concomitant ingestion with carbohydrates, up to 60% better, which may further be related to increased insulin concentration (Green et al., Am J. Physiol. 1996 271:E821-6). Furthermore, glucose and Creatine uptake by muscle cells has been shown to be stimulated by insulin (Odoom et al., Mol Cell Biochem. 1996 158:179-88). Thus, the ingestion of Creatine combined with a source of carbohydrates is recommended to improve retention. It may also be beneficial to include a source of protein at the time of Creatine ingestion (Steenge et al., J Appl Physiol. 2000 89:1165-71).

U.S. Pat. No. 5,767,159 purports to describe a method for increasing muscle capacity and replenishing ATP by administering daily Creatine in healthy mammals. The amount of said Creatine is at least 0.2-0.4 g per kg body weight and not less than 15 g in a 70 kg mammal to be taken for at least 2 days but not more than 7 days. The Creatine is administered in solution which may further include other conventional nutrients such as lipids, carbohydrates, amino acids, electrolytes, trace elements and vitamins.

U.S. Pat. No. 5,968,544 purports to describe compositions containing Creatine for human consumption suitable for use in a drink or as dry powder stable for storage. The Creatine is provided in an acidic yogurt-based semi-liquid composition or forms an acidic solution when mixed with water.

U.S. Pat. No. 5,973,199 purports to describe compositions for water soluble Creatine salts usable in foods.

U.S. Pat. No. 5,968,900 purports to describe compositions and methods for increasing Creatine and glycogen concentration in muscle by increasing blood plasma insulin concentration. In one described embodiment, the compositions described are composed of Creatine or Creatine derivatives with a carbohydrate, wherein the carbohydrate is said to cause an increase in blood plasma insulin levels, which results in increases in Creatine retention.

In an embodiment of the present invention, which is set forth in greater detail in the examples below, the dietary supplement includes Creatine or derivatives thereof. A serving of the dietary supplement may include from about 3 g to about 15 g of Creatine or derivatives thereof. The preferred dosage of a serving of the dietary supplement comprises about 10 g of Creatine or derivatives thereof.

Taurine

Taurine, an amino acid found primarily in nerve and muscle tissue, is generally considered to be a conditionally-essential amino acid, being only required under certain circumstances. As it is not utilized for protein synthesis, Taurine is found in the free form or in some small peptides. The accumulation of Taurine within cells is mediated via a high affinity sodium-dependent transporter (Ramamoorthy et al., Biochem J. 1994 300:893-900). The expression of this Taurine transporter is induced by differentiation program of myocytes (muscle cells) (Uozumi et al., Biochem J. 2006 394:699-706). Exercise-induced hormones also known to activate the Taurine transporter (Park et al., Biofactors. 2004 21:403-6). Moreover, genetically modified mice lacking the Taurine transporter have depleted Taurine levels in all muscle and have impaired skeletal muscle function (Warskulat et al., FASEB J. 2004 18:577-9)

One of the main roles of Taurine is the regulation of fluid balance and is released by contracting muscles (Cuisinier et al., Eur J Appl Physiol. 2002 87:489-95). Taurine has also been shown to modulate the contractile function of mammalian skeletal muscle (Bakker et al., J. Physiol. 2002 538:185-94). In rats, the Taurine concentration in muscle decreases as a result of exercise (Matsuzaki et al., Med Sci Sports Exerc. 2002 34:793-7) and oral supplementation with Taurine has been shown to maintain the concentration of Taurine in muscle and prolong exercise performance (Miyazaki et al., Amino Acids. 2004 27:291-8; Yatabe et al., J Orthop Sci. 2003; 8:415-9).

In a model of spontaneous diabetes, Taurine supplementation has been shown to improve insulin sensitivity in rats (Nakaya et al., Am J Clin Nutr. 2000 71:54-8). Furthermore, Taurine improves glucose metabolism in insulin resistant rats (Nandhini et al., Amino Acids. 2002; 22:27-38), suggesting that Taurine has insulin-like properties which may improve Creatine uptake and retention within muscle cells. Supplementation with Taurine has additionally been shown to reduce exercise-induced oxidative damage and enhance recovery (Zhang et al., Amino Acids. 2004 26:203-7).

In an embodiment of the present invention, which is set forth in greater detail in the examples below, the dietary supplement includes Taurine or derivatives thereof. A serving of the dietary supplement may include from about 0.5 g to about 3 g of Taurine or derivatives thereof. The preferred dosage of a serving of the dietary supplement comprises about 2.1 g of Taurine or derivatives thereof.

Phosphate

Phosphate, or phosphorus, is the second most abundant mineral in the body with calcium being the most abundant. As a Phosphate salt with calcium, Phosphate is involved in the formation of bone and teeth. In other salt complexes, Phosphate is involved in acid-base balance. Phosphate is also important for the structures of DNA and cell membranes. One of the most important roles of Phosphate is energy production in muscle as ATP and Phosphocreatine. Phosphate is also part of a compound in red blood cells known as 2,3 DPG (2,3-diphosphoglycerate), which facilitates the release of oxygen to the muscle tissues.

Supplemental Phosphate salts have been shown to increase the concentration of 2,3 DPG in red blood cells, increasing VO2 max (a measure of aerobic fitness) and a reduction in the production of lactate (Cade et al., Med Sci Sports Exerc. 1984 16:263-8). Moreover, Phosphate has also been shown to enhance oxygen uptake and run performance without affecting the level of 2,3 DPG (Kreider et al., Med Sci Sports Exerc. 1990 22:250-6).

The metabolic rate can also be increased by Phosphate supplementation (Nazar et al., J Physiol Pharmacol. 1996 47:373-83).

In an embodiment of the present invention, which is set forth in greater detail in the examples below, the dietary supplement includes a source of Phosphate or derivatives thereof. A serving of the dietary supplement may include from about 0.1 g to about 1.5 g of Phosphate or derivatives thereof. The preferred dosage of a serving of the dietary supplement comprises about 0.18 g of elemental Phosphate or derivatives thereof.

Alpha Lipoic Acid

Alpha Lipoic Acid (ALA) is an enzyme found in the cellular energy-producing structures, the mitochondria. ALA works in synergy with vitamins C and E as an antioxidant in both the water- and fat-soluble environments.

In rats supplemented with ALA the negative age-related changes in mitochondrial function, accumulated oxidative damage and metabolic rate were all improved (Hagen et al., FASEB J. 1999 13:411-8). As such, the antioxidant activity of ALA is likely involved in the prevention of cell death due to an improvement in oxidative stress (Arivazhagan et al., Pharmacol Res. 2000 41:299-303). Furthermore, ALA has been linked to a beneficial increase in high-density lipoproteins (Wollin et al., J Nutr Biochem. 2004 15:402-10) possibly due to its known effects as an antioxidant.

Additionally, ALA appears to possess a dual action related to hunger and >oxidation of fat. First, the activity of AMP-activated protein kinase, which acts as an energy sensor in the hypothalamus, is reduced by ALA in rodents, this results in a profound weight loss by reducing food intake and enhancing energy expenditure (Kim et al., Nat Med. 2004 10:727-33). Second, ALA increases Uncoupling Protein-1 in rodent adipocytes while increasing AMP-activated protein kinase in skeletal muscle cells and increasing glucose uptake and energy expenditure (Lee et al., Int J Biochem Cell Biol. 2005 37:2254-9). Therefore, ALA seemingly has different effects in different tissues.

However, in adipocytes or muscle cells ALA increases fatty acid oxidation, leading to an increase in energy expenditure and a decrease in weight and food intake.

U.S. Pat. Nos. 6,136,339 and 6,620,425 disclose compositions and methods for enhancing an athlete's muscle size or strength using a combination of Creatine, Alpha Lipoic Acid and optionally Dextrose, to be taken mixed with water daily following exercise.

In an embodiment of the present invention, which is set forth in greater detail in the examples below, the dietary supplement may include Alpha Lipoic Acid or derivatives thereof. A serving of the dietary supplement may include from about 0.005 g to about 0.4 g of Alpha Lipoic Acid or derivatives thereof. The preferred dosage of a serving of the dietary supplement comprises about 0.25 g of Alpha Lipoic Acid or derivatives thereof.

Dextrose

Dextrose is a simple sugar or monosaccharide commonly known as D-glucose. Also known as ‘grape sugar’ or ‘blood sugar’, it is found mainly in honey and fruits and is a building-block of glycogen, cellulose and starch. Recently, Dextrose was shown to boost the performance a female rowers as compared to ribose, which had been theorized to replenish muscle energy (Dunne et al., Clin J Sport Med. 2006 16:68-71).

In an embodiment of the present invention, which is set forth in greater detail in the examples below, the dietary supplement may include Dextrose. A serving of the dietary supplement may include from about 50 g to about 100 g of Dextrose. The preferred dosage of a serving of the dietary supplement comprises about 75 g of Dextrose.

Mulberry Extract

Mulberry (Morus alba) is an edible plant used in Chinese medicine which is rich in flavonoids possessing antioxidant activity (Doi et al. Chem Pharm Bull (Tokyo). 2001 49:151-3). Orally administered mulberry extracts of Mulberry reduced blood glucose levels of both non-diabetic and streptozotocin-treated diabetic rats, commensurate with decreased food intake (Musabayane et al., Methods Find Exp Clin Pharmacol. 2006 28:223-8). Orally consumed extracts of Mulberry have also been shown to inhibit increases in blood glucose resulting from the ingestion of carbohydrates such as sucrose in humans and rats (Oku et al., Br J. Nutr. 2006 95:933-8). Furthermore, extracts of Mulberry confer neuroprotective benefits (Kang et al., Biol Pharm Bull. 2006 29:270-4) and may further attenuate the development of atherosclerotic lesions (Enkhmaa et al., J. Nutr. 2005 135:729-34).

In an embodiment of the present invention, which is set forth in greater detail in the examples below, the dietary supplement may include Mulberry extract. A serving of the dietary supplement may include from about 0.01 g to about 0.05 g of Mulberry extract. The preferred dosage of a serving of the dietary supplement comprises about 0.025 g of Mulberry extract.

Chromium

Chromium is an essential trace mineral that is used to control blood sugar levels by aiding insulin, which can help control or reduce weight. Chromium is poorly absorbed by the body and must therefore be combined with a more efficiently absorbed compound such as niacin as in the case of polynicotinate. Chromium likely exerts its main function as a component or a co-factor of the glucose tolerance factor, which is involved in insulin sensitivity.

Chromium has been shown clinically to increase lean mass (Bahadori et al., Acta Med Austriaca. 1997 24:185-7) and reduce body fat when combined with exercise (Grant et al., Med Sci Sports Exerc. 1997 29:992-8). Moreover, chromium has also been shown to increase high density lipoproteins (HDL i.e. ‘good’ cholesterol) (Riales et al., Am J Clin Nutr 1981; 34:2670-8). Numerous clinical studies have demonstrated the relationship between supplemental Chromium and improved insulin activity and glucose metabolism (Anderson, Diabetes Metab. 2000 26:22-7).

In an embodiment of the present invention, which is set forth in greater detail in the examples below, the dietary supplement may include a derivative of Chromium. A serving of the dietary supplement may include from about 0.001 g to about 0.005 g of a derivative of Chromium. The preferred dosage of a serving of the dietary supplement comprises about 0.003 g of a derivative of Chromium.

Glutamine

Glutamine is the most abundant amino acid found in muscle and has important functions as a precursor for the synthesis of other amino acids. Many cells required for immune function rely on Glutamine as source for energy production.

Physical activity can deplete Glutamine levels, and as such, Glutamine is often considered to be a ‘conditionally essential’ amino acid. A study examining the Glutarine levels of groups involved in several different types of activities or sports found that powerlifters and swimmers had lower Glutamine levels than cyclists and non-athletes (Hiscock and Mackinnon, Med Sci Sports Exerc. 1998 30:1693-6), suggesting that high resistance load activities require increased amounts of Glutamine. Moreover, this depletion of Glutamine has been linked to immunosuppression often resulting from intense training (Newsholme, Int J Sports Med. 1994 15:S142-7). Supplementation with Glutamine in conjunction with additional antioxidants can increase body weight, body cell mass and intracellular water when compared with placebo (Shabert et al., Nutrition. 1999 15:860-4). Glutamine is also capable of stimulating insulin secretion (Tanizawa et al., Diabetes. 2002 51:712-7).

In an embodiment of the present invention, which is set forth in greater detail in the examples below, the dietary supplement may include Glutamine or a derivative thereof. A serving of the dietary supplement may include from about 0.001 g to about 0.005 g of Glutamine or a derivative thereof. The preferred dosage of a serving of the dietary supplement comprises about 0.002 g of Glutamine or a derivative thereof.

Enicostemma littorale Blume

Enicostemma littorale Blume is a flower-producing herb found in South America, Africa, and Asia. In rat models of diabetes, Enicostemma littorale extract can enhance glucose-induced insulin release thereby effectively lowering blood glucose levels (Maroo et al., J. Ethnopharmacol. 2002 81:317-20; Maroo et al., Phytomedicine. 2003 10:196-9).

Furthermore, Enicostemma littorale extract counters the changes in several metabolic enzymes and antioxidants observed in diabetic rats, including lowering thiobarbituric acid reactive substances and lipid hydroperoxides while increasing the concentration of reduced glutathione and the activities of superoxide dismutase and catalase (Srinivasan et al., J Pharm Pharmacol. 2005 57:497-503). The lipid profile of rats fed cholesterol was also improved by administration of Enicostemma littorale extract (Vasu et al., J. Ethnopharmacol. 2005 101:277-82).

In an embodiment of the present invention, which is set forth in greater detail in the examples below, the dietary supplement may include Enicostemma littorale Blume. A serving of the dietary supplement may include from about 0.0005 g to about 0.003 g of Enicostemma littorale Blume. The preferred dosage of a serving of the dietary supplement comprises about 0.001 g of Enicostemma littorale Blume.

Scoparia dulcis (Scotch brum)

Scoparia dulcis is a tropical herb found in abundance in South America and the Amazon rainforest and has been used traditionally for multiple treatments including diabetes. Extracts of Scoparia dulcis provide both antidiabetic and antihyperlipidemic actions in normal and experimentally diabetic rats (Pari and Latha, J Med Food. 2006 9:102-7). Scoparia dulcis extract has also demonstrated antioxidant and neuroprotective activity (Pari and Latha, BMC Complement Altem Med. 2004 4:16).

In an embodiment of the present invention, which is set forth in greater detail in the examples below, the dietary supplement may include Scoparia dulcis. A serving of the dietary supplement may include from about 0.0005 g to about 0.003 g of Scoparia dulcis. The preferred dosage of a serving of the dietary supplement comprises about 0.001 g of Scoparia dulcis.

Tarragon extract (Artemisia dracunculus)

Russian Tarragon (Artemisia dracunculus) is a perennial herb widely used in cooking. Historically, it has been used as a natural blood cleanser and as a treatment for headaches and dizziness. Current studies are examining the use of an ethanolic extract of Russian Tarragon for the treatment of hyperglycemia associated with diabetes. The toxicology of this extract has been evaluated, and has been shown to be safe and non-toxic (Ribnicky et al., Food Chem Toxicol. 2004 42:585-98). Essential oil extracted from Artemisia dracunculus may also have potential as an anticonvulsant and as a mild sedative (Sayyah et al., J. Ethnopharmacol. 2004 94:283-7).

In an embodiment of the present invention, which is set forth in greater detail in the examples below, the dietary supplement may include Tarragon extract. A serving of the dietary supplement may include from about 0.0005 g to about 0.003 g of Tarragon extract. The preferred dosage of a serving of the dietary supplement comprises about 0.001 g of Tarragon extract.

Andrographis paniculata

Andrographis paniculata is a medicinal herb used traditionally throughout Asia to treat a number of conditions. Clinical studies have demonstrated an immunity-enhancing benefit of Andrographis paniculata supplementation by reducing the occurrence and severity of common cold symptoms (Caceres et al., Phytomedicine. 1999 6:217-23) and upper-respiratory tract infections (Melchior et al., Phytomedicine. 2000 7:341-50).

Additionally, Andrographis paniculata has been shown to possess antipyretic, fever-reducing, activity similar to that of aspirin (Vedavathy and Rao, J. Ethnopharmacol. 1991 33:193-6). Furthermore, Andrographis paniculata has been shown to reduce chemically-induced liver toxicity in experimental mice (Kapil et al., Biochem Pharmacol. 1993 46:182-5).

Andrographis paniculata extract possesses antihyperglycaemic and antioxidative activities in both normal and chemically-induced diabetic rats (Zhang and Tan, Clin Exp Pharmacol Physiol. 2000 27:358-63). The antidiabetic properties of Andrographis paniculata are believed to be due at least in part to enhanced glucose metabolism (Zhang and Tan, Acta Pharmacol Sin. 2000 21:1157-64).

In an embodiment of the present invention, which is set forth in greater detail in the examples below, the dietary supplement may include Andrographis paniculata. A serving of the dietary supplement may include from about 0.0005 g to about 0.003 g of Andrographis paniculata. The preferred dosage of a serving of the dietary supplement comprises about 0.001 g of Andrographis paniculata.

Double Fermented Triticum aestivum

Double Fermented Triticum aestivum is a whole-grain wheat product low in simple sugars and high in complex carbohydrates. This produces a more level glucose/insulin response rather than the typical “spike” resulting from simple sugar ingestion. As such, Double Fermented Triticum aestivum is marketed towards overweight or obese individuals or individuals with impaired glucose tolerance. Double Fermented Triticum aestivum was found effective at reducing the risks associated with development of type 2 diabetes such as elevated fasting blood glucose levels and obesity (Rave et al., 65^(th) Annual Scientific Sessions, American Diabetes Association 2005, Abstract 1765-P).

In an embodiment of the present invention, which is set forth in greater detail in the examples below, the dietary supplement may include Double Fermented Triticum aestivum. A serving of the dietary supplement may include from about 0.05 g to about 0.3 g of Double Fermented Triticum aestivum. The preferred dosage of a serving of the dietary supplement comprises about 0.1 g of Double Fermented Triticum aestivum.

Isomalt

Isomalt is a disaccharide sugar substitute derived from sucrose which is less sweet than, and is often mixed with, more conventional sweeteners. Being only partially digested in the intestines, isomalt results in a low blood glucose effect, has benefits similar to that of dietary fiber, and has a caloric value of about half that of sugar. Moreover, Isomalt has been shown to promote healthy bowel function without impairing metabolic function (Gostner et al., Br J. Nutr. 2005 94:575-81; Gostner et al. Br J. Nutr. 2006 95:40-50).

In an embodiment of the present invention, which is set forth in greater detail in the examples below, the dietary supplement may include Isomalt. A serving of the dietary supplement may include from about 0.0005 g to about 0.003 g of Isomalt. The preferred dosage of a serving of the dietary supplement comprises about 0.001 g of Isomalt.

Trehalose

Trehalose is a naturally occurring disaccharide found in plants, invertebrates and fungi and is about half as sweet as sucrose or table sugar. Trehalose has been discovered to be able to inhibit the aggregation of some proteins and thus has potential in the prevention of diseases linked to such events such as Huntington's disease (Tanaka et al., Nat Med. 2004 10:148-54).

In an embodiment of the present invention, which is set forth in greater detail in the examples below, the dietary supplement may include Trehalose. A serving of the dietary supplement may include from about 0.0005 g to about 0.003 g of Trehalose. The preferred dosage of a serving of the dietary supplement comprises about 0.001 g of Trehalose.

D-Mannose

Mannose is a monosaccharide found in some fruits including cranberry. It is absorbed slowly in the gastrointestinal tract, with most being excreted in the urine. D-mannose has been theorized to aid in the treatment of urinary tract infections by virtue of being able to bind to the surface proteins of infection-causing bacteria, thereby facilitating their clearance (Schaeffer et al., J. Urol. 1984 131:906-10).

In an embodiment of the present invention, which is set forth in greater detail in the examples below, the dietary supplement may include D-mannose. A serving of the dietary supplement may include from about 0.0005 g to about 0.003 g of D-mannose. The preferred dosage of a serving of the dietary supplement comprises about 0.001 g of D-mannose.

According to various embodiments of the present invention, the dietary supplement may be consumed in any form. For instance, the dosage form of the dietary supplement may be provided as, e.g., a powder beverage mix, a liquid beverage, a ready-to-eat bar or drink product, a capsule, a liquid capsule, a tablet, a caplet, or as a dietary gel. The preferred dosage form of the present invention is as a powder beverage mix or a drink product.

Fine-Milling of Active Constituents

As set forth above, the dosage form of the dietary supplement, in accordance with the example embodiments set forth below, may be provided in accordance with customary processing techniques for herbal and/or dietary supplements, wherein the active ingredients are suitably processed into a desired form. In accordance with various embodiments of the present invention, one or more ingredients of the diet supplement are processed so as to form fine-milled particles. For instance, in various embodiments, one or more ingredients of the dietary supplemental are processed by a large-scale dry milling technique that produces fine particles, preferably known as fine-milled particles. The use of dry milling techniques, in combination with excipients and polymers, to form fine-milled particles has been shown to improve flow and dispersability, stability, resistance to moisture, bioavailability, and dissolution/release properties. Formulations benefit by containing fine-milled particles for the purpose of providing the one or more ingredients in particle sizes that optimize one or more of the flow and dispersability, stability, resistance to moisture, bioavailability, and dissolution/release properties of the one or more ingredients in a dietary supplement. In vitro tests designed to simulate the environment of stomach were preformed to test the dissolution rate of fine-milled particle tablets versus non-fine-milled. These test showed that in tablets produced from fine-milled particles the time to 100% dissolution was approximately 15 minutes. In the case of non-fine-milled particle compositions, only 90% dissolution was observed after 120 minutes. In preferred embodiments, the dietary supplemental contains fine-milled particles having and average size between about 50 nm and about 2 nm.

U.S. Provisional Patent Application 60/776,325 discloses a method for improving the absorption, palatability, taste, texture, and bioavailability of compounds by increasing the solubility of said compounds in proprietary formulations for the purposes of enhancing or improving muscle size, growth and/or recovery time and/or weight loss. The increased bioavailability of the compound or ingredients is achieved by reducing the particle size via “fine-milling” thereby increasing the surface area-to-volume ratio each particle, thus increasing the rate of dissolution. The compositions and methods disclosed promote increased bioavailability by increasing the total surface area of poorly soluble particles, thereby increasing the rate of absorption.

As used herein the, term “fine-milled” and/or “fine-milling” refers to the process of micronization. Micronization is a mechanical process that involves the application of force to a particle, thereby resulting in a reduction in the size of the particle. The force, in the case of micronization may be applied in any manner such as, e.g., the collision of particles at high rates of speed, grinding, or by an air-jet micronizer. In preferred embodiments, fine-milled particles are obtained by jet-milling with nitrogen and compressed air.

As used herein, term “particle size” refers to the diameter of the particle. The term “average particle size” means that at least 50% of the particles in a sample will have the specified particle size. Preferably, at least 80% of the particles in a sample will have the specified particle size, and more preferably, at least 90% of the particles in a given sample will have the specified particle size.

The size of a particle can be determined any of the methods known within the art. Methods for particle size determination which may be employed are for example, e.g., sieves, sedimentation, electrozone sensing (Coulter counter), microscopy, and/or Low Angle Laser Light Scattering. The preferred methods for the particle size determination of the present invention are those methods which are most commonly used in the pharmaceutical industry, such as laser diffraction, e.g., via light scattering Coulter Delsa 440SX.

The fine-milling process may be employed in the processing of one or more of the ingredients of the present invention in the dosage forms of tablets, e.g., immediate-release film coated, modified-release and fast-dissolving; capsules or tablets, e.g., immediate-release and modified-release; liquid dispersions; powders; drink mixes, etc.

Preferably, the dietary supplement of the present invention is consumed by an individual in accordance with the following method: As a dietary supplement, a serving of said dietary supplement may be taken by means of mixing in about 360-450 ml of an acceptable aqueous fluid at least one (1) time daily wherein each serving is comprised of two (2) scoops comprising about 100 g total mass of the dietary supplement. Said dietary supplement may be consumed approximately 0 to 60 minutes following a workout, or in the morning upon waking on non-workout days. In this manner, the dietary supplement may increase Creatine uptake and retention in skeletal muscle, increase muscle mass and strength, increase exercise capacity and aid in post-exercise recovery as well as provide support for the immune system during intense exercise training periods

Furthermore, the dosage form of the supplemental composition may be provided in accordance with customary processing techniques for herbal and dietary supplements in any of the forms mentioned above. Additionally, the dietary supplement set forth in the example embodiments herein may contain any appropriate number and type of excipients, as is well-known in the art.

The present dietary supplement or those similarly envisioned by one of skill in the art, may be utilized in compositions and methods for increasing Creatine uptake and retention in skeletal muscle, increasing muscle mass and strength, increasing exercise capacity and aiding in post-exercise recovery as well as providing support for the immune system during intense exercise training periods of an individual, e.g. a human or an animal in a formulation designed to be consumed at least one time per day.

Although the following examples illustrate the practice of the present invention in three of its various embodiments, the examples should not be construed as limiting the scope of the invention. Other embodiments will be apparent to one skilled in the art from consideration of the specification and example.

EXAMPLE 1

A serving of the dietary supplement comprises the following ingredients in powdered beverage mix form. The dietary supplement comprises for example: about 74 g of pharma grade Dextrose 99 DE, about 9 g of Creatine monohydrate, finely grinded, about 2.1 g of Taurine, about 0.33 g of Dipotassium Phosphate, about 0.33 g of Magnesium Phosphate, about 0.26 g of Sodium Alpha Lipoic Acid, about 0.025 g of and extract of Mulberry, about 0.003 g of Chromium polynicotinate, about 0.001 g of Anhydrous Creatine, about 0.001 g of Taurine ethyl ester HCl, about 0.001 g of Glutamine AKG 2:1, about 0.001 g of Glutamine ethyl ester HCl, about 0.001 g of Enicostemma littorale Blume, about 0.001 g of Scoparia dulcis, about 0.001 g of an extract of Tarragon, about 0.001 g of Andrographis paniculata.

Directions: As a dietary supplement, 2 scoops, comprising about 100 g total mass of the dietary supplement are administered by a means of mixing said dietary supplement in 360-450 ml of an acceptable aqueous fluid at least one (1) time daily. Said serving is to be consumed approximately 0 to 60 minutes following a workout or in the morning upon waking on non-workout days.

EXAMPLE 2

A serving of the dietary supplement comprises the following ingredients in powdered beverage mix form. The dietary supplement comprises for example: about 75 g of pharma grade Dextrose 99 DE, about 9 g of finely grinded Creatine monohydrate, about 2.1 g of Taurine, about 1 g of fine-milled Creatine monohydrate, about 0.33 g of Dipotassium Phosphate, about 0.33 g of Disodium Phosphate, about 0.26 g of the Sodium salt of Alpha Lipoic Acid, about 0.025 g of an extract of Mulberry, about 0.003 g of Chromium polynicotinate, about 0.001 of Anhydrous Creatine, about 0.001 g of Dicreatine malate, about 0.001 g of Creatine HCA salt, about 0.001 g of Taurine ethyl ester HCl, about 0.001 g of Glutamine AKG 2:1, about 0.001 g of Glutamine ethyl ester HCl, about 0.001 g of Enicostemma littorale Blume, about 0.001 g of Scoparia dulcis, about 0.001 g of an extract of Tarragon extract, and about 0.001 g of Andrographis paniculata.

Directions: As a dietary supplement, 2 scoops, comprising about 100 g total mass of the dietary supplement are administered by a means of mixing said dietary supplement in 360-450 ml of an acceptable aqueous fluid at least one (1) time daily. Said serving is to be consumed approximately 0 to 60 minutes following a workout or in the morning upon waking on non-workout days.

EXAMPLE 3

A serving of the dietary supplement comprises the following ingredients in powdered beverage mix form. The dietary supplement comprises for example: about 75 g of pharma grade Dextrose 99 DE, about 9 g of finely grinded Creatine monohydrate, about 2.1 g of Taurine, about 1 g of fine-milled Creatine monohydrate, about 0.33 g of Dipotassium Phosphate, about 0.33 g of Disodium Phosphate, about 0.33 g of Magnesium Phosphate, about 0.26 g of Sodium Alpha Lipoic Acid, about 0.1 g of Double Fermented Triticum aestivum, about 0.025 g of an extract of Mulberry, about 0.003 g of Chromium polynicotinate, about 0.001 g of Anhydrous Creatine, about 0.001 g of Creatine Dicreatine malate, about 0.001 g of Creatine pyroglutamate, about 0.001 g of Creatine HCA salt, about 0.001 g of Taurine ethyl ester HCl, about 0.001 g of Glutamine AKG 2:1, about 0.001 g of Glutamine ethyl ester HCl, about 0.001 g of Enicostemma littorale Blume, about 0.001 g of Scoparia dulcis, about 0.001 g of and extract of Tarragon, about 0.001 g of Andrographis paniculata, about 0.001 g of Isomalt, about 0.001 g of Trehalose, about 0.001 g of D-mannose.

Directions: As a dietary supplement, 2 scoops, comprising about 100 g total mass of the dietary supplement are administered by a means of mixing said dietary supplement in 360-450 ml of an acceptable aqueous fluid at least one (1) time daily. Said serving is to be consumed approximately 0 to 60 minutes following a workout or in the morning upon waking on non-workout days.

Extensions and Alternatives

In the foregoing specification, the invention has been described with specific embodiments thereof, however, it will be evident that various modifications and changes may be made thereto without departing from the broader spirit and scope of the invention.

All publications which are cited herein are hereby specifically incorporated by reference into the disclosure for the teachings for which they are cited. 

1. A composition comprising: Creatinol-O-phosphate; at least one substance selected from the group consisting of Taurine or derivatives thereof, glutamine or derivatives thereof, an extract of Mulberry, Chromium, Enicostemma littorle Blume, Scoparia dulcis, an extract of Tarragon, Andrographis paniculata, Chromium, and Alpha Lipoic Acid; at least one source of phosphate selected from the group consisting of Dipotassium Phosphate, Disodium Phosphate and Magnesium Phosphate; and a source of carbohydrates.
 2. The composition of claim 1, wherein the source of carbohydrates comprises at least one of monosaccharides, disaccharides, oligosaccharides, polysaccharides or derivatives thereof.
 3. The composition of claim 1 further comprising creatine or derivative thereof.
 4. A composition comprising: Creatinol-O-phosphate; Glutamine AKG; Dipotassium Phosphate; Disodium Phosphate; and a polysaccharide.
 5. A composition comprising: Creatinol-O-phosphate; Taurine; Dipotassium Phosphate; Disodium Phosphate; and a polysaccharide.
 6. The composition of claim 4, further comprising Dicreatine malate. 